This review focuses on the advancements in manganese (Mn) complex-based magnetic resonance imaging (MRI) agents for imaging different diseases. Here we emphasize the unique redox properties of Mn to deliver innovative MRI contrast agents, including small molecules, nanoparticles (NPs), metal–organic frameworks (MOFs), and polymer hybrids. Aspects of their rational design have been discussed, including size dependence, morphology tuning, surface property enhancement, etc., while also discussing the existing challenges and potential solutions. The present work will inspire and motivate scientists to emphasize MRI-guided applications and bring clinical success in the coming years.

The progress in nanobiohybrids empowered by modified bacteria and vesicles for cancer treatment is systematically updated.

Taking advantages of weak light scattering and minimal amount of auto-fluorescence background, optical imaging through the second near-infrared window (NIR-II, 1000-1700 nm) allows resolving the microscopic structures in deep tissues. However, current 2D wide-field imaging systems cannot provide the axial resolution to reveal depth information and the lateral resolution thereof has been limited by the pixel numbers of NIR-II cameras. We aim to improve 3D in vivo imaging at a large field of view (FOV) to achieve high-resolution 3D imaging of bone and vessel simultaneously. We developed a 3D NIR-II imaging technique utilizing iterative convolutional sub-pixel image reconstruction (ICSP-IR) and convolutional neural networks (CNN) in a binocular system. The instrumentation and CNN powered data analytics enable 3D in vivo volumetric imaging with a lateral resolution of 153 µm and an axial resolution of 480 µm at a FOV of 42.5 mm × 53 mm × 14 mm. High-resolution 3D imaging of both tibia structures and vessel networks can be simultaneously achieved by the 808-nm and 980-nm dual-beam excitations of NIR-Ⅱa type nanoparticles that emit at 1060 nm and NIR-Ⅱb type nanoparticles that emit at 1530 nm, respectively.

Photochromic glass shows great promise for 3D optical information encryption and storage applications. The formation of Ag nanoclusters by light irradiation has been a significant development in the field of photochromic glass research. However, extending this approach to other metal nanoclusters remains a challenge. In this study, we present a pioneering method for crafting photochromic glass with reliably adjustable dual-mode luminescence in both the NIR and visible spectra. This was achieved by leveraging bimetallic clusters of bismuth, resulting in a distinct and novel photochromic glass. When rare-earth-doped, bismuth-based glass is irradiated with a 473 nm laser, and it undergoes a color transformation from yellow to red, accompanied by visible and broad NIR luminescence. This phenomenon is attributed to the formation of laser-induced (Bi+, Bi-0) nanoclusters. We achieved reversible manipulation of the NIR luminescence of these nanoclusters and visible rare-earth luminescence by alternating exposure to a 473 nm laser and thermal stimulation. Information patterns can be inscribed and erased on a glass surface or in 3D space, and the readout is enabled by modulating visible and NIR luminescence. This study introduces a pioneering strategy for designing photochromic glasses with extensive NIR luminescence and significant potential for applications in high-capacity information encryption, optical data storage, optical communication, and NIR imaging. The exploration of bimetallic cluster formation in Bi represents a vital contribution to the advancement of multifunctional glass systems with augmented optical functionalities and versatile applications.

Abstract Skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (μCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.

Bone health related skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Light excitation and optical imaging through the near-infrared-II window (NIR-II, 1000-1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can be passively transported by endothelial cells and macrophages from the blood vessels into bone marrow microenvironment. We found that this passive targeting scheme can be effective for longer than two months. We therefore developed an intravital 3D and high-resolution planar imaging instrumentation for bone disease diagnosis. We demonstrated the regular monitoring of 1 mm bone defects for over 10 days, with resolution similar to X-ray imaging result, but more flexible use in prognosis. Moreover, the passive targeting can be used to reveal the early onset inflammation at the joints as the synovitis in the early stage of rheumatoid arthritis. Furthermore, the proposed method is comparable to {\mu}CT in recognizing symptoms of osteoarthritis, including the mild hyperostosis in femur which is ~100 {\mu}m thicker than normal, and the growth of millimeter-scale osteophyte in the knee joint, which further proves the power and universality of our approach in diagnosis of bone diseases

Fluorescence imaging through the second near-infrared window (NIR-II,1000–1700 nm) allows in-depth imaging. However, current imaging systems use wide-field illumination and can only provide low-contrast 2D information, without depth resolution. Here, we systematically apply a light-sheet illumination, a time-gated detection, and a deep-learning algorithm to yield high-contrast high-resolution volumetric images. To achieve a large FoV (field of view) and minimize the scattering effect, we generate a light sheet as thin as 100.5 μm with a Rayleigh length of 8 mm to yield an axial resolution of 220 µm. To further suppress the background, we time-gate to only detect long lifetime luminescence achieving a high contrast of up to 0.45 Ιcontrast. To enhance the resolution, we develop an algorithm based on profile protrusions detection and a deep neural network and distinguish vasculature from a low-contrast area of 0.07 Ιcontrast to resolve the 100 μm small vessels. The system can rapidly scan a volume of view of 75 × 55 × 20 mm3 and collect 750 images within 6 mins. By adding a scattering-based modality to acquire the 3D surface profile of the mice skin, we reveal the whole volumetric vasculature network with clear depth resolution within more than 1 mm from the skin. High-contrast large-scale 3D animal imaging helps us expand a new dimension in NIR-II imaging.

Background: Currently, the prognosis and survival rate for patients bearing non-small cell lung cancer (NSCLC) is still quite poor, mainly due to lack of efficient theranostic paradigms to exert in time diagnostics and therapeutics. Methods: Herein, for NSCLC treatment, we offer a customized theranostic paradigm, termed NIR-IIb fluorescence diagnosis and synergistic surgery/starvation/chemodynamic therapeutics, with a newly designed theranostic nanoplatform PEG/MnCuDCNPs@GOx. The nanoplatform is composed of brightly NIR-II emissive downconversion nanoparticles (DCNPs)-core and Mn/Cu-silica shell loaded with glucose oxidase (GOx) to achieve synergistic starvation and chemodynamic therapy (CDT). Results: It is found that 10% Ce3+ doped in the core and 100% Yb3+ doped in the middle shell greatly improves the NIR-IIb emission up to even 20.3 times as compared to the core-shell DCNPs without Ce3+ doping and middle shell. The bright NIR-IIb emission of the nanoplatform contributes to sensitive margin delineation of early-stage NSCLC (diameter < 1 mm) with a signal-to-background ratio (SBR) of 2.18, and further assists in visualizing drug distribution and guiding surgery/starvation/chemodynamic therapy. Notably, the starvation therapy mediated by GOx-driven oxidation reaction efficiently depletes intratumoral glucose, and supplies H2O2 to boost the CDT mediated by the Mn2+ and Cu2+, which consequently realized a highly effective synergistic treatment for NSCLC. Conclusion: This research demonstrates an efficient treatment paradigm for NSCLC with NIR-IIb fluorescence diganosis and image-guided synergistic surgery/starvation/chemodynamic therapeutics.

The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a physical barrier to regulate and prevent the uptake of endogenous metabolites and xenobiotics. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. Therefore, there is considerable interest in identifying drug carriers that can maintain the biostability of therapeutic molecules and target their transport across the BBB. In this regard, upconversion nanoparticles (UCNPs) have become popular as a nanoparticle-based solution to this problem, with the additional benefit that they display unique properties for in vivo visualization. The majority of studies to date have explored basic spherical UCNPs for drug delivery applications. However, the biophysical properties of UCNPs, cell uptake and BBB transport have not been thoroughly investigated. In this study, we described a one-pot seed-mediated approach to precisely control longitudinal growth to produce bright UCNPs with various aspect ratios. We have systematically evaluated the effects of the physical aspect ratios and PEGylation of UCNPs on cellular uptake in different cell lines and an in vivo zebrafish model. We found that PEGylated the original UCNPs can enhance their biostability and cell uptake capacity. We identify an optimal aspect ratio for UCNP uptake into several different types of cultured cells, finding that this is generally in the ratio of 2 (length/width). This data provides a crucial clue for further optimizing UCNPs as a drug carrier to deliver therapeutic agents into the CNS. STATEMENT OF SIGNIFICANCE: The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a highly selective semipermeable barrier of endothelial cells to regulate and prevent the uptake of toxins and pathogens. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. The proposed research is significant because identifying the aspect ratio of drug carriers that maintains the biostability of therapeutic molecules and targets their transport across the blood-brain barrier (BBB) is crucial for designing an efficient drug delivery system. Therefore, this research provides a vital clue for further optimizing UCNPs as drug carriers to deliver therapeutic molecules into the brain.

Conventional biomedical imaging modalities, including endoscopy, X-rays, and magnetic resonance, are invasive and insufficient in spatial and temporal resolutions for gastrointestinal (GI) tract imaging to guide prognosis and therapy. Here we report a noninvasive method based on lanthanide-doped nanocrystals with ∼1530 nm fluorescence in the near-infrared-IIb window (NIR-IIb, 1500-1700 nm). The rational design of nanocrystals have led to an absolute quantum yield (QY) up to 48.6%. Further benefiting from the minimized scattering through the NIR-IIb window, we enhanced the spatial resolution to ∼1 mm in GI tract imaging, which is ∼3 times higher compared with the near-infrared-IIa (NIR-IIa, 1000-1500 nm) method. The approach also realized a high temporal resolution of 8 frames per second; thus the moment of mice intestinal peristalsis can be captured. Furthermore, with a light-sheet imaging system, we demonstrated a three-dimensional (3D) imaging on the GI tract. Moreover, we successfully translated these advances to diagnose inflammatory bowel disease.

Video-rate super-resolution imaging through biological tissue can visualize and track biomolecule interplays and transportations inside cellular organisms. Structured illumination microscopy allows for wide-field super resolution observation of biological samples but is limited by the strong extinction of light by biological tissues, which restricts the imaging depth and degrades its imaging resolution. Here we report a photon upconversion scheme using lanthanide-doped nanoparticles for wide-field super-resolution imaging through the biological transparent window, featured by near-infrared and low-irradiance nonlinear structured illumination. We demonstrate that the 976 nm excitation and 800 nm upconverted emission can mitigate the aberration. We found that the nonlinear response of upconversion emissions from single nanoparticles can effectively generate the required high spatial frequency components in the Fourier domain. These strategies lead to a new modality in microscopy with a resolution below 131 nm, 1/7th of the excitation wavelength, and an imaging rate of 1 Hz.

Thermally responsive fluorescent nanoparticles can be constructed to allow robust, rapid, and noninvasive temperature measurements. Furthermore, due to their tiny size, they can be used to detect temperature changes at the nanoscale. In this way, such sensors are ideally suited to emerging applications including intracellular temperature sensing and microelectronics failure diagnostics. Despite their potential, current nanothermometers still suffer from limited sensitivity, dynamic range, and stability. By introducing thermal enhanced anti-Stokes emission from a pair of lanthanide ions, ytterbium and neodymium, we show an increase of more than 1 order of magnitude in both the sensitivity and the dynamic range when compared to conventional ytterbium and erbium-codoped nanothermometers. Here, we report heterogeneous temperature-responsive nanoparticles with a new record of sensitivity (9.6%/K at room temperature and above 2.3%/K at elevated temperatures up to 413 K) that can be used for ratiometric thermometry. The heterogeneous nanostructure design shows that the thermal responses can be fine-tuned by the controlled growth of nanoparticles. The stability of the ultrasensitive nanothermometers has enabled long-term noncontact monitoring of local heat dissipation of a microelectronic device.

Nanoparticles with anti-Stokes emissions have enabled many sensing applications, but their efficiencies are considerably low. The key to enable the process of anti-Stokes emissions is to create phonons that assist the excited photons to be pumped from a lower energy state onto a higher one. Increasing the temperature will generate more phonons, but it unavoidably quenches the luminescence. Here by quantifying the number of phonons being generated from the host crystal and those at the surface of Yb3+/Nd3+ co-doped nanoparticles, we systematically investigated mechanisms towards the large enhancements of the phonon-assisted anti-Stokes emissions from 980 nm to 750 nm and 803 nm. Moreover, we provided direct evidence that moisture release from the nanoparticle surface at high temperature was not the main reason. We further demonstrated that the brightness of 10 nm nanoparticles was enhanced by more than two orders of magnitude, in stark contrast to the thermal quenching effect.

Thermal quenching, in which light emission experiences a loss with increasing temperature, broadly limits luminescent efficiency at higher temperature in optical materials, such as lighting phosphors1–3 and fluorescent probes4–6. Thermal quenching is commonly caused by the increased activity of phonons that leverages the non-radiative relaxation pathways. Here, we report a kind of heat-favourable phonons existing at the surface of lanthanide-doped upconversion nanomaterials to combat thermal quenching. It favours energy transfer from sensitizers to activators to pump up the intermediate excited-state upconversion process. We identify that the oxygen moiety chelating Yb3+ ions, [Yb···O], is the key underpinning this enhancement. We demonstrate an approximately 2,000-fold enhancement in blue emission for 9.7 nm Yb3+-Tm3+ co-doped nanoparticles at 453 K. This strategy not only provides a powerful solution to illuminate the dark layer of ultra-small upconversion nanoparticles, but also suggests a new pathway to build high-efficiency upconversion systems. Phonons on the surface of lanthanide-doped upconversion materials are used to combat thermal quenching, enabling ~2,000-fold emission enhancement.

Kinetic or thermodynamic control has been employed to guide the selective synthesis of conventional organic compounds, and it should be a powerful tool as well for accessing unusual inorganic nanocrystals, particularly when a series of members with similar chemical compositions and phase structures exist. Indeed, a comprehensive mapping of the energy barrier distribution of each nanocrystal in a predefined reaction system will enable not only the precise synthesis of nanocrystals with expected sizes, morphologies, phase structures, and ultimately functionalities, but also disclosure of the evolution details of nanocrystals from one structure to another. Using ScFx:Ln (x = 2.76, 3) series as a proof-of-concept, we have successfully mapped out the energy barriers that correspond to each of the ScFx:Ln nanocrystals, unraveled suitable temperatures for each type of nanocrystal formation, recorded their phase transition procedures, and also discovered the relationships of the products at each reaction stage. To testify how this approach allows one to tailor the structure-related optical properties, different lanthanide-doped ScFx nanocrystals were synthesized and a wide-range of luminescence fine-tuning was achieved, which not only showcases high quality of the nanocrystals, but also provides more candidates for various luminescence applications, especially when single-particle upconversion emission is required.

Sensitivity is the key in optical detection of low-abundant analytes, such as circulating RNA or DNA. The enzyme Exonuclease III (Exo III) is a useful tool in this regard; its ability to recycle target DNA molecules results in markedly improved detection sensitivity. Lower limits of detection may be further achieved if the detection background of autofluorescence can be removed. Here we report an ultrasensitive and specific method to quantify trace amounts of DNA analytes in a wash-free suspension assay. In the presence of target DNA, the Exo III recycles the target DNA by selectively digesting the dye-tagged sequence-matched probe DNA strand only, so that the amount of free dye removed from the probe DNA is proportional to the number of target DNAs. Remaining intact probe DNAs are then bound onto upconversion nanoparticles (energy donor), which allows for upconversion luminescence resonance energy transfer (LRET) that can be used to quantify the difference between the free dye and tagged dye (energy acceptor). This scheme simply avoids both autofluorescence under infrared excitation and many tedious washing steps, as the free dye molecules are physically located away from the nanoparticle surface, and as such they remain "dark" in suspension. Compared to alternative approaches requiring enzyme-assisted amplification on the nanoparticle surface, introduction of probe DNAs onto nanoparticles only after DNA hybridization and signal amplification steps effectively avoids steric hindrance. Via this approach, we have achieved a detection limit of 15 pM in LRET assays of human immunodeficiency viral DNA.

A series of Ce3+, Eu2+, and Eu3+ activated yttrium silicate calcium oxyapatite phosphors were prepared via sol-gel technique with citric acid as a chelating agent for the metal ions. The X-ray diffraction spectra of these materials were investigated and the results in different host lattice were compared. The photoluminescence spectra were discussed and the effects of the crystal structure of the host on the spectroscopic behavior were addressed. When excited by ultraviolet light, Ce3+, Eu2+, and Eu3+ activated yttrium silicate calcium phosphors emit intense blue, green and red light, respectively. The potential applications of these compounds in the white-light emitting diodes were discussed. In this work, we have obtained white-light by mixing the Ce3+, Eu2+, and Eu3+ activated yttrium silicate calcium phosphors in a certain mass ratio.

La2W2O9:2%Eu3+ phosphors were synthesized by a typical hydrothermal procedure. The samples were characterized by X-ray diffraction and scanning electron microscope (SEM). X-ray diffraction analysis showed that a stock solution pH value equal to 9 is the ideal value, while the crystallization of the hydroxyl sodium yttrium tungstate crystal is improved by increasing the PH values of stock solution within limits. Meanwhile, SEMs of different pH values were recorded. Additionally, photo-luminescence excitation (PLE) and emission (PL) spectra were measured. It was found that this phosphor can be effectively excited by C-T band (266 nm) and ultraviolet light 342 nm. The wave-lengths at 342 nm fit in nicely with the whole visible region, thus the La2W2O9:2%Eu3+ phosphors emit white light. Furthermore, the annealing temperature's impact on PLE and PL spectra was also studied. The Eu3+-doped La2W2O9 phosphor may be a better candidate than current method for solid-state lighting applications.